Serum iron level and kidney function: a Mendelian randomization study

Del Greco M., Fabiola, Foco, Luisa, Pichler, Irene, Eller, Philipp, Eller, Kathrin, Benyamin, Beben, Whitfield, John B., Genetics of Iron Status Consortium, CKDGen Consortium, Pramstaller, Peter P., Thompson, John R., Pattaro, Cristian and Minelli, Cosetta (2016) Serum iron level and kidney function: a Mendelian randomization study. Nephrology, Dialysis, Transplantation, 32 2: 273-278. doi:10.1093/ndt/gfw215


Author Del Greco M., Fabiola
Foco, Luisa
Pichler, Irene
Eller, Philipp
Eller, Kathrin
Benyamin, Beben
Whitfield, John B.
Genetics of Iron Status Consortium
CKDGen Consortium
Pramstaller, Peter P.
Thompson, John R.
Pattaro, Cristian
Minelli, Cosetta
Title Serum iron level and kidney function: a Mendelian randomization study
Journal name Nephrology, Dialysis, Transplantation   Check publisher's open access policy
ISSN 0931-0509
1460-2385
Publication date 2016-06-02
Sub-type Article (original research)
DOI 10.1093/ndt/gfw215
Open Access Status Not yet assessed
Volume 32
Issue 2
Start page 273
End page 278
Total pages 6
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 2727 Nephrology
2747 Transplantation
Abstract Background: Iron depletion is a known consequence of chronic kidney disease (CKD), but there is contradicting epidemiological evidence on whether iron itself affects kidney function and whether its effect is protective or detrimental in the general population. While epidemiological studies tend to be affected by confounding and reverse causation, Mendelian randomization (MR) can provide unconfounded estimates of causal effects by using genes as instruments. Methods: We performed an MR study of the effect of serum iron levels on estimated glomerular filtration rate (EGFR), using genetic variants known to be associated with iron.MR estimates of the effect of iron on EGFR were derived based on the association of each variant with iron and EGFR from two large genome-wide meta-analyses on 48 978 and 74 354 individuals. We performed a similar MR analysis for ferritin, which measures iron stored in the body, using variants associated with ferritin. Results: A combined MR estimate across all variants showed a 1.3% increase in EGFR per standard deviation increase in iron (95% confidence interval 0.4-2.1%; P = 0.004). The results for ferritin were consistent with those for iron. Secondary MR analyses of the effects of iron and ferritin on CKD did not show significant associations but had very low statistical power. Conclusions: Our study suggests a protective effect of iron on kidney function in the general population. Further research is required to confirm this causal association, investigate it in study populations at higher risk of CKD and explore its underlyingmechanismof action.
Formatted abstract
Background: Iron depletion is a known consequence of chronic kidney disease (CKD), but there is contradicting epidemiological evidence on whether iron itself affects kidney function and whether its effect is protective or detrimental in the general population. While epidemiological studies tend to be affected by confounding and reverse causation, Mendelian randomization (MR) can provide unconfounded estimates of causal effects by using genes as instruments.

Methods: We performed an MR study of the effect of serum iron levels on estimated glomerular filtration rate (eGFR), using genetic variants known to be associated with iron. MR estimates of the effect of iron on eGFR were derived based on the association of each variant with iron and eGFR from two large genome-wide meta-analyses on 48 978 and 74 354 individuals. We performed a similar MR analysis for ferritin, which measures iron stored in the body, using variants associated with ferritin.

Results: A combined MR estimate across all variants showed a 1.3% increase in eGFR per standard deviation increase in iron (95% confidence interval 0.4–2.1%; P = 0.004). The results for ferritin were consistent with those for iron. Secondary MR analyses of the effects of iron and ferritin on CKD did not show significant associations but had very low statistical power.

Conclusions: Our study suggests a protective effect of iron on kidney function in the general population. Further research is required to confirm this causal association, investigate it in study populations at higher risk of CKD and explore its underlying mechanism of action.
Keyword Mendelian randomization
Chronic kidney disease
Ferritin
Glomerular filtration rate
Iron
Kidney function
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Created: Wed, 28 Sep 2016, 02:25:09 EST by Kirstie Asmussen on behalf of School of Music